The objective of this research is to develop quantitative susceptibility mapping (QSM) for the detection of intraplaque hemorrhage (IPH) in rupture-prone carotid atherosclerotic plaque. Compared to carotid plaque without IPH, IPH increases the risk of stroke by 4 to 6-fold. Accurate detection of carotid IPH is critically important for stroke risk stratification to distinguish patients who are at high risk and would benefit from carotid surgery or stenting to prevent stroke, from those with lower risk who would derive similar risk reduction benefit from noninvasive medication treatment alone. Our scientific premise is that QSM can resolve paramagnetic IPH hemosiderin from diamagnetic calcification, both appearing hypointense on traditional multi-contrast MRI (mcMRI). IPH is identified as hyperintensity on T1-weighted images, which corresponds to the transient methemoglobin phase of hemorrhage. In the immediately ensuing hemosiderin phase, however, IPH appears hypointense due to the strong susceptibility-induced dephasing effects of the superparamagnetic hemosiderin (magnetic susceptibility>150 ppm). This hypointensity on T1-weighted and other mcMRI images is typically regarded as calcification, another common component of the carotid plaque with diamagnetic magnetic susceptibility (-2.3 ppm). Contrary to IPH, which is a marker for plaque instability, calcification indicates plaque stability and reduces the risk of cerebral embolization by nearly 50%. Therefore, the inability of traditional mcMRI to differentiate IPH from calcification prevents accurate stroke risk stratification. We will develop carotid plaque QSM to directly measure magnetic susceptibility and to overcome the inherent inability of T1-weighted imaging to distinguish between IPH hemosiderin and calcification. We have pioneered QSM development and demonstrated the exquisite sensitivity of QSM for hemorrhagic iron. We also have substantial clinical experience with imaging of high-risk carotid plaque. In this project, we will develop a novel 3D carotid QSM pulse sequence with efficient conic k-space sampling to achieve high isotropic resolution and with fat navigator for robust motion compensation. We will validate the developed QSM sequence by comparing with the gold standard of post-surgery imaging and histopathology. A successful outcome of this research will establish QSM as a powerful imaging biomarker to differentiate intraplaque hemorrhage and calcification for stroke prevention.